Preface

There are many patients who are suffering from various types of vascular diseases. Atherosclerosis results in luminal narrowing and insufficient blood perfusion, leading to organ damage such as myocardial infarction, cerebral infarction, and amputation of lower extremities. Atherosclerotic diseases are a leading cause of death in industrialized countries. Obstructive atherosclerotic diseases are treated by percutaneous catheter intervention or bypass surgery, which requires subsequent re-vascularization procedures due to re-stenosis of the target lesion or a bypass graft in many cases. Aortic aneurysm and cerebral aneurysm may cause sudden death by unanticipated rupture. Graft vasculopathy—diffuse intimal hyperplasia in arteries of the transplanted organs—causes grant failure. Moreover, coronary aneurysm is the major sequel of Kawasaki’s disease, a mucocutaneous lymph node syndrome in children. Unfortunately, exact pathogenesis of most of the vascular diseases remains to be clarified. Subsequently, there are no established methods to diagnose and prevent those vascular diseases accurately. Genetically modified mice are a very powerful tool for studying the pathogenesis of various diseases, including immunology, oncology, the central nervous system, autoimmune disease, and congenital diseases. Genetically modified mice also provide good tools to track the origin and the fate of the cells that play a key role in the disease process. However, mice had always been thought to be too small to be used for research in the field of vascular diseases. Most of the models of vascular diseases, which have been used for larger animals, could not be applied to mice. I have been working as an interventional cardiologist. I treated many patients with coronary artery diseases by performing percutaneous coronary intervention (PCI). However, re-stenosis at the site of PCI limited the long-term prognosis of the treatment in many patients. Therefore, I started research on gene therapy to prevent post-PCI re-stenosis. However, no gene therapy has been shown to be effective enough to be used in clinical practice. When I became an independent researcher in Japan in 1999, I realized that we should clarify the exact pathogenesis of re-stenosis using genetically modified mice. I had a hard time developing a mouse model of post-angioplasty re-stenosis. After many efforts and failures, I finally succeeded in